Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection
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Updated: May 9, 2026
A Rat Model of EcoHIV Brain Infection
Published on: January 21, 2021
Christine Fennema-Notestine1, Ronald J Ellis, Sarah L Archibald
1Department of Psychiatry, University of California, San Diego, CA 92093-0738, USA. fennema@ucsd.edu
Abstract:
MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79 % initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis.
Insights
Brain MRI changes in HIV infection are linked to immune recovery. Greater CD4+ T cell recovery correlated with increased abnormal white matter and subcortical gray matter volumes, suggesting neuroinflammation.
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Cerebral white matter (WM) and gray matter (GM) alterations are frequent in HIV infection, persisting even with combination antiretroviral therapy (CART).
- The underlying pathophysiology and clinical relevance of these MRI-detected brain changes remain incompletely understood.
Purpose of the Study:
- To investigate the association between MRI-defined cerebral alterations and CD4+ T cell recovery in individuals with HIV.
- To explore the relationship between these brain changes and virologic suppression.
Main Methods:
- Seventy-five HIV-positive volunteers underwent serial brain MRI scans.
- Multi-channel morphometry was used to quantify volumes of cerebral WM, abnormal WM, cortical and subcortical GM, and cerebrospinal fluid (CSF) spaces.
- Multivariable linear regression models analyzed the correlation between volumetric changes and CD4+ T cell count changes, alongside HIV RNA levels.
Main Results:
- The cohort experienced overall loss of total cerebral WM, with concurrent increases in abnormal WM and ventricular volumes.
- Enhanced recovery of CD4+ T cells was significantly associated with increased volumes of abnormal WM and subcortical GM.
- Virologic suppression independently correlated with increased subcortical GM volume.
Conclusions:
- Brain structural changes in HIV-infected individuals may be linked to immune reconstitution, separate from virologic control.
- The observed increases in abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggest neuroinflammation as a potential mechanism in HIV central nervous system (CNS) pathogenesis.
